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• W2898841798 abstract "Microtubules are tubulin polymer structures, which are indispensable for cell growth and division. Its constituent protein β-tubulin has been a common drug target for various diseases including cancer. Colchicine has been used to treat gout, but it has also been an investigational anticancer agent with a known antimitotic effect on cells. However, the use of colchicine as well as many of its derivatives in long-term treatment is hampered by their high toxicity. To create more potent anticancer agents, three novel double-modified colchicine derivatives have been obtained by structural modifications in C-4 and C-10 positions. The binding affinities of these derivatives of colchicine with respect to eight different isotypes of human β-tubulin have been calculated using docking methods. In vitro cytotoxicity has been evaluated against four human tumor cell lines (A549, MCF-7, LoVo and LoVo/DX). Computer simulations predicted the binding modes of these compounds and hence the key residues involved in the interactions between tubulin and the colchicine derivatives. Two of the obtained derivatives, 4-bromothiocolchicine and 4-iodothiocolchicine, were shown to be active against three of the investigated cancer cell lines (A549, MCF-7, LoVo) with potency at nanomolar concentrations and a higher relative affinity to tumor cells over normal cells." @default.
• W2898841798 created "2018-11-09" @default.
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• W2898841798 date "2018-11-01" @default.
• W2898841798 modified "2023-10-02" @default.
• W2898841798 title "Antiproliferative Activity and Molecular Docking of Novel Double-Modified Colchicine Derivatives" @default.
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• W2898841798 doi "https://doi.org/10.3390/cells7110192" @default.
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